The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

// Anja Pickhard 1,* , Michael Siegl 1,* , Alexander Baumann 1 , Maximilian Huhn 1 , Markus Wirth 1 , Rudolf Reiter 2 , Martina Rudelius 3 , Guido Piontek 1 and Gero Brockhoff 4 1 Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany 2 Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany 3 Institute of Pathology, Julius-Maximilians-University and Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany 4 Department of Gynecology and Obstetrics; University of Regensburg, Regensburg, Germany * Equal contribution Correspondence: Anja Pickhard, email: // Keywords : Aurora kinase A polymorphism, Aurora kinase B, cetuximab, HNSCC Received : May 1, 2014 Accepted : June 17, 2014 Published : June 18, 2014 Abstract Objectives: The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines. Materials and methods: First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples. The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting. Results: Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27). Conclusion: This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.